The present invention relates to coated granules containing pharmacological active principles whose unpleasant gustatory properties are masked both by complexation by a cation-exchange resin and by coating. It also relates to orodispersible tablets containing such coated granules.
It is known to complex pharmacologically active substances that have disagreeable gustatory qualities, such as a bitter taste, by combining them with cation-exchange resins. Thus, U.S. Pat. No. 6,193,962, U.S. Pat. No. 5,811,436 and U.S. Pat. No. 6,514,492; disclose liquid pharmaceutical formulations that contain active principles complexed by a crosslinked polymethacrylic acid resin, in suspension in an aqueous phase. U.S. Pat. No. 5,219,563 discloses uncoated dry granules of a bitter active principle (ranitidine) complexed by crosslinked polymethacrylic acid.
In the context of its research aiming to develop orodispersible tablets of active substances for which it is necessary to mask the unpleasant taste, the applicant has however observed that, for a certain number of substances that are particularly bitter and/or that leave a burning sensation in the mouth, such as fluoxetine, the simple masking of the taste by complexing with a cation-exchange resin was insufficient.
It is furthermore widely known in the art to mask the unpleasant taste of certain active principles by coating with gastrosoluble polymers. In the case of substances such as fluoxetine that have a very pronounced bitter flavor and leave a burning sensation in the mouth, such masking by coating is however relatively ineffective and requires polymer amounts that are too large. Thus, the coating of fluoxetine with 50 wt % of polymer is barely enough to mask the bitterness of the molecule and amounts ranging beyond this value do not make it possible to obtain dissolution kinetics in an acid medium that conforms to the specifications of the USP monograph for fluoxetine tablets which requires a dissolution rate greater than 85 wt % in 15 minutes in a 0.1 N HCl solution.
There is therefore still a need for orodispersible tablets of pharmacologically active substances that have particularly unpleasant gustatory qualities, which combine both good taste masking and rapid release of the active principle in an acid medium.